Randomized Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00557830
• Collaborator: Bayer (Industry)
• Enrollment: 12
• Locations: 13
• Arms: 2
• Duration (Months): 39
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the effectiveness of a dose-escalation regimen (400 to 800mg bid) relative to the standard dosing regimen (400mg bid) of sorafenib given in patients with metastatic RCC.

The secondary objectives are to evaluate the effects of the dose-escalation regimen on the quality of life (QoL) of patients with metastatic RCC and to characterize the safety and tolerability profile of a dose-escalation regimen of sorafenib in patients with metastatic RCC.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma	Drug: Sorafenib Escalated Dose; Drug: Sorafenib Standard Dose	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase IIb Study of Sorafenib Dose Escalation in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (RCC)
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A: Escalated Dose Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Drug: Sorafenib Escalated Dose; Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.; Other Names: Nexavar
Active Comparator: Group B: Standard Dose Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.	Drug: Sorafenib Standard Dose; Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.; Other Names: Nexavar

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. [Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.]

   Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.

Secondary Outcome Measures

1. PFS Rate at 9, 13 and 17 Months [PFS was to be measured at 9, 13, and 17 months.]

   Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.

2. Overall Survival Rate [Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.]

   Due to the early study closure and the small sample size, overall survival rate was not evaluated.

3. Changes From Baseline in Symptom Burden [The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.]

   The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment. The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥18 years old.

• Diagnosis of unresectable/metastatic renal cell carcinoma (RCC). Nonclear cell histology is permitted (except for medullary, collecting duct, or sarcomatoid >50% of specimen). Prior metastasectomy is permitted as long as there is measurable disease at time of consent.

• Karnofsky Performance Status of 50% or greater at study entry.

• Adequate bone marrow, liver and renal function as assessed by the following: o Hemoglobin ≥ 9.0 g/dL. o ANC ≥ 1500/mm3. o Platelet count ≥ 100,000/mm3. o Total bilirubin ≤ 1.5 ULN. o ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver involvement). o Creatinine ≤ 1.5 × ULN.

• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to the start of treatment.

• Women of childbearing potential and sexually active men must agree to use adequate barrier contraception prior to study entry, for the duration of study participation, and for at least three months after the last administration of sorafenib.

• INR < 1.5 or a PT/ PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

• Prior systemic anticancer treatment for metastatic disease, including investigational therapy.

• Prior treatment with bevacizumab, sunitinib, or sorafenib even in the adjuvant setting.

• Prior cytokine therapy with interleukin (IL)-2 or interferon (IFN) for metastatic disease.

• Active malignancy other than RCC (except non-melanoma skin cancer) within 5 years of enrollment.

• Hemodialysis or peritoneal dialysis.

• Treatment with radiotherapy within 2 weeks of enrollment.

• Cardiac disease: Congestive heart failure Class II or higher per NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.

• Uncontrolled CNS metastases. All patients must undergo a CT) scan/MRI of the brain to exclude brain metastasis. Patients with adequately treated CNS disease may be considered for participation as long as the first dose of sorafenib is 4 weeks after completion of CNS therapy.

• Uncontrolled hypertension defined as SBP > 150 mmHg or DBP > 90 mmHg, despite optimal medical management.

• Active clinically serious infection > Grade 2 per the CTCAE v3.

• Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• Pulmonary hemorrhage/bleeding event ≥ Grade 2 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.

• Any other hemorrhage/bleeding event ≥ Grade 3 per CTCAE v3.0 within 4 weeks of administration of the first dose of study drug.

• Serious non-healing wound, ulcer, or bone fracture.

• Evidence or history of bleeding diathesis or coagulopathy.

• Major surgery, open biopsy or significant traumatic injury within 4 weeks of administration of the first study drug dose.

• Use of St. John's Wort, rifampin (rifampicin), phenytoin, Phenobarbital, carbamazepine, dexamethasone.

• Known or suspected allergy to sorafenib or any agent given in the course of this trial.

• Any condition that impairs patient's ability to swallow whole pills.

• Any malabsorption problem.

• Pregnancy or lactation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clopton Clinic	Jonesboro	Arkansas	United States	72401
2	Wilshire Oncology Medical Group, Inc.	La Verne	California	United States	91750
3	Advanced Medical Specialties	Miami	Florida	United States	33176
4	Northeast Georgia Cancer Care	Athens	Georgia	United States	30607
5	Peachtree Hematology Oncology Consultants	Atlanta	Georgia	United States	30309
6	Central Georgia Cancer Care	Macon	Georgia	United States	31201
7	Northwest Georgia Oncology Centers	Marietta	Georgia	United States	30060
8	Mid-Illinois Hematology and Oncology Associates, Ltd.	Normal	Illinois	United States	61761
9	Hematology Oncology Centers of the Northern Rockies	Billings	Montana	United States	59101
10	Gaston Hematology and Oncology	Gastonia	North Carolina	United States	28054
11	Pacific Oncology, PC	Beaverton	Oregon	United States	97006
12	The Lancaster Cancer Center, Ltd	Lancaster	Pennsylvania	United States	17605
13	The West Clinic	Memphis	Tennessee	United States	38120

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• Bayer

Investigators

• Principal Investigator: Vasily Assikis, MD, Acorn Cardiovascular, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00557830
• Other Study ID Numbers: AVJARCC0702
• First Posted: Nov 14, 2007
• Last Update Posted: Jul 18, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Accelerated Community Oncology Research Network: Renal Cell Carcinoma; Kidney Cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Sorafenib

Study Results

Participant Flow

Recruitment Details	13 community oncology sites across the US associated with the ACORN network participated in this study. Enrollment started in January 2008 and was closed in August 2008 due to the low rate of accrual and lack of funds beyond the current level of support from Bayer.
Pre-assignment Detail	Informed consent was obtained from all subjects. All subjects underwent a screening phase that could last up to 4 weeks during which pre-study assessments were completed. Eligible subjects then underwent a screening treatment phase in which they received commercial sorafenib for 4 weeks.

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Period Title: Screening Treatment Phase
STARTED	12	0	0
COMPLETED	6	0	0
NOT COMPLETED	6	0	0
Period Title: Screening Treatment Phase
STARTED	0	4	2
COMPLETED	0	4	2
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose	Total
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.	Total of all reporting groups
Overall Participants	12	4	2	18
Age (years) [Mean (Standard Deviation) ]
Screening Treatment Phase	62.2 (10.99)	NA (NA)	NA (NA)	62.2 (10.99)
Randomization Phase	NA (NA)	66.0 (6.38)	58.5 (7.78)	63.5 (7.18)
Sex/Gender, Customized (Number) [Number]
Female (Screening Treatment Phase)	3 25%	0 0%	0 0%	3 16.7%
Male (Screening Treatment Phase)	9 75%	0 0%	0 0%	9 50%
Female (Randomization Phase)	0 0%	2 50%	0 0%	2 11.1%
Male (Randomization Phase)	0 0%	2 50%	2 100%	4 22.2%
Region of Enrollment (participants) [Number]
United States	NA NaN	NA NaN	NA NaN	0 0%
Region of Enrollment, Customized (participants) [Number]
United States (Screening Treatment Phase)	12 100%	NA NaN	NA NaN	12 66.7%
United States (Randomization Phase)	NA NaN	4 100%	2 100%	6 33.3%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (CR + PR) Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Description	Response was evaluated via changes from baseline in radiological tumor measurements performed every 8 weeks and at the end of treatment unless clinically indicated prior to that. Confirmatory scans were to be obtained no less than 4 weeks but no more than 6 weeks following initial documentation of objective response. Response was evaluated using RECIST criteria, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease; Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions or the appearance of one or more new lesions.
Time Frame	Overall response will be measured at baseline and every 8 weeks , unless clinically indicated prior to that, until the end of treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Measure Participants	0	4	2
Complete Response (CR)	0 0%	0 0%
Partial Response (PR)	0 0%	0 0%
Stable Disease (SD)	3 25%	1 25%
Progressive Disease (PD)	1 8.3%	1 25%

2. Secondary Outcome

Title	PFS Rate at 9, 13 and 17 Months
Description	Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.
Time Frame	PFS was to be measured at 9, 13, and 17 months.

Outcome Measure Data

Analysis Population Description

Due to the early study closure and the small sample size, the PFS rate at 9, 13, and 17 months were not evaluated.

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Measure Participants	0	0	0

3. Secondary Outcome

Title	Overall Survival Rate
Description	Due to the early study closure and the small sample size, overall survival rate was not evaluated.
Time Frame	Overall survival was measured from day 1 of treatment until the end of treatment and then every 4 months thereafter until death.

Outcome Measure Data

Analysis Population Description

Due to the early study closure and the small sample size, overall survival rate was not evaluated.

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Measure Participants	0	0	0

4. Secondary Outcome

Title	Changes From Baseline in Symptom Burden
Description	The Patient Care Monitor Version 2.0 (PCM) is an tablet computer based assessment system that measures patient reported outcomes (PROs) in medical patients with a particular emphasis on symptoms related to cancer and its treatment. The PCM comprises 86 items which include 8 items answered only by females (e.g. menstrual cramping). Each item is presented so that the patient rates the degree to which the item has been a problem in the past week (0 not a problem to 10 as bad as possible).
Time Frame	The PCM was administered during screening, at each scheduled visit (approximately every 4 weeks), and at the end of treatment visit.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Measure Participants	12	4	2
Hives (Welts)-Baseline	0 (0)	0 (0)	0 (0)
Hives (Welts)-Post-BL	1.2 (2.94)	0.2 (0.38)	0 (0)
Sinus Problem-Baseline	1.1 (2.51)	2.3 (3.86)	0 (0)
Sinus Problem-Post-BL	1.1 (1.89)	2.4 (2.54)	0.1 (0.11)
Chest Pain-Baseline	0.1 (0.32)	0.3 (0.5)	0 (0)
Chest Pain-Post-BL	0.3 (0.56)	0.4 (0.54)	0 (0)
Rapid Heart Beat-Baseline	0.8 (2.53)	2 (4)	0 (0)
Rapid Heart Beat-Post-BL	0.3 (0.75)	0.9 (1.2)	0 (0)
Swelling-Baseline	0.3 (0.95)	0.8 (1.5)	0 (0)
Swelling-Post-BL	1 (2.28)	0 (0.06)	0 (0)
Constitutional Chills-Baseline	0.2 (0.63)	0.5 (1)	0 (0)
Constitutional Chills-Post-BL	0.9 (1.69)	0.8 (1.32)	0 (0)
Fatigue-Baseline	2.3 (2.54)	3.8 (3.3)	2 (2.83)
Fatigue-Post-BL	2.7 (2.72)	5 (3.22)	0.5 (0.71)
Fever-Baseline	0.4 (1.26)	1 (2)	0 (0)
Fever-Post-BL	0.9 (1.47)	1.4 (2)	0 (0)
Weight Gain-Baseline	1.3 (2.75)	1.8 (3.5)	0 (0)
Weight Gain-Post-BL	0.3 (0.78)	0 (0)	0 (0)
Weight Loss-Baseline	0.4 (1.26)	1 (2)	0 (0)
Weight Loss-Post-BL	0.7 (1.39)	1.6 (2.14)	0 (0)
Change In Taste-Baseline	0.5 (1.27)	1 (2)	0 (0)
Change In Taste-Post-BL	0.8 (1.41)	2.2 (1.81)	0 (0)
Difficulty Hearing-Baseline	0.7 (2.21)	1.8 (3.5)	0 (0)
Difficulty Hearing-Post-BL	0.5 (1.24)	0 (0)	0 (0)
Dry Mouth-Baseline	0.8 (2.04)	0 (0)	0 (NA)
Dry Mouth-Post-BL	1.7 (1.5)	2 (1.7)	2.7 (NA)
Mouth Sores/Ulcers-Baseline	0.1 (0.32)	0 (0)	0 (0)
Mouth Sores/Ulcers-Post-BL	0.9 (1.53)	0.6 (1.04)	0 (0)
Sore Throat-Baseline	0 (0)	0 (0)	0 (0)
Sore Throat-Post-BL	0.4 (0.63)	0.5 (0.54)	0 (0)
Trouble Swallowing-Baseline	0 (0)	0 (0)	0 (0)
Trouble Swallowing-Post-BL	0.3 (0.62)	0.3 (0.5)	0 (0)
Day Sweat-Baseline	0 (0)	0 (0)	0 (0)
Day Sweat-Post-BL	0 (0)	0 (0)	0 (0)
Hot Flashes/Flushes-Baseline	0 (0)	0 (0)	NA (NA)
Hot Flashes/Flushes-Post-BL	0 (0)	0 (0)	NA (NA)
Night Sweat-Baseline	1.7 (3.65)	4.3 (5.06)	0 (0)
Night Sweat-Post-BL	0.4 (1.3)	1.1 (2.25)	0 (0)
Reduced Sexual Enjoyment-Baseline	0.2 (0.63)	0 (0)	0 (0)
Reduced Sexual Enjoyment-Post-BL	0.4 (1.08)	0.9 (1.75)	0 (0)
Dry Eyes-Baseline	0.7 (2)	1.5 (3)	0 (0)
Dry Eyes-Post-BL	0.9 (1.49)	1.4 (1.79)	0 (0)
Tearing-Baseline	1.1 (1.96)	2.3 (2.63)	0 (0)
Tearing-Post-BL	0.5 (1.36)	1.2 (2.35)	0 (0)
Trouble Seeing-Baseline	0.4 (1.33)	1 (2)	0 (0)
Trouble Seeing-Post-BL	1.6 (2.9)	2 (3.37)	0 (0)
Constipation-Baseline	0.1 (0.32)	0.3 (0.5)	0 (0)
Constipation-Post-BL	0.2 (0.45)	0.5 (0.71)	0.3 (0.35)
Decrease in Appetite-Baseline	0 (0)	0 (0)	0 (0)
Decrease in Appetite-Post-BL	0.8 (1.89)	2.4 (2.87)	0 (0)
Diarrhea-Baseline	0 (0)	0 (0)	0 (0)
Diarrhea-Post-BL	0.8 (0.88)	1.1 (0.77)	1.3 (1.88)
Heartburn-Baseline	0.7 (1.25)	1.3 (1.89)	0 (0)
Heartburn-Post-BL	1.2 (1.67)	2.7 (2.17)	0 (0)
Increase in Appetite-Baseline	0.1 (0.32)	0 (0)	0 (0)
Increase in Appetite-Post-BL	0.2 (0.48)	0.1 (0.14)	0 (0)
Nausea-Baseline	0.1 (0.32)	0 (0)	0 (0)
Nausea-Post-BL	0.8 (1.11)	1.4 (1.53)	0.5 (0.71)
Vomiting-Baseline	0 (0)	0 (0)	0 (0)
Vomiting-Post-BL	0.4 (0.86)	1.1 (1.31)	0 (0)
Menstrual Pain/Cramping-Baseline	0 (0)	0 (0)	NA (NA)
Menstrual Pain/Cramping-Post-BL	0 (0)	0 (0)	NA (NA)
Problem with Urination-Baseline	0.5 (1.08)	1.3 (1.5)	0 (0)
Problem with Urination-Post-BL	0.2 (0.48)	0 (0)	0 (0)
Vaginal Bleeding-Baseline	0 (0)	0 (0)	NA (NA)
Vaginal Bleeding-Post-BL	0 (0)	0 (0)	NA (NA)
Vaginal Discharge-Baseline	0 (0)	0 (0)	NA (NA)
Vaginal Discharge-Post-BL	0.1 (0.14)	0.1 (0.18)	NA (NA)
Vaginal Dryness-Baseline	0 (0)	0 (0)	NA (NA)
Vaginal Dryness-Post-BL	0 (0.07)	0.1 (0.09)	NA (NA)
Vaginal Itching-Baseline	0 (0)	0 (0)	NA (NA)
Vaginal Itching-Post-BL	0.5 (0.51)	0.2 (0.27)	NA (NA)
Bleeding-Baseline	0.2 (0.63)	0 (0)	0 (0)
Bleeding-Post-BL	0.1 (0.17)	0.1 (0.25)	0 (0)
Bruising-Baseline	0.2 (0.63)	0 (0)	0 (0)
Bruising-Post-BL	0.4 (1.35)	0 (0)	0 (0)
New Lump/Mass-Baseline	0 (0)	0 (0)	0 (0)
New Lump/Mass-Post-BL	0.2 (0.79)	0.7 (1.38)	0 (0)
Breast Tenderness-Baseline	0 (0)	0 (0)	NA (NA)
Breast Tenderness-Post-BL	0 (0)	0 (0)	NA (NA)
Dry Skin-Baseline	1.4 (2.99)	2 (4)	3 (4.24)
Dry Skin-Post-BL	2.5 (3.34)	3.2 (2.72)	0.2 (0.33)
Hair Loss-Baseline	0 (0)	0 (0)	0 (0)
Hair Loss-Post-BL	1.2 (1.86)	3.3 (1.9)	0.5 (0.65)
Itching-Baseline	1.1 (2.33)	1.3 (2.5)	3 (4.24)
Itching-Post-BL	1.7 (2.78)	1.2 (0.85)	0.1 (0.19)
Nails Change-Baseline	0 (0)	0 (0)	0 (0)
Nails Change-Post-BL	0.7 (1.27)	1.9 (1.62)	0.1 (1.6)
Nipple Discharge-Baseline	0 (0)	0 (0)	NA (NA)
Nipple Discharge-Post-BL	0 (0)	0 (0)	NA (NA)
Rash-Baseline	0 (0)	0 (0)	0 (0)
Rash-Post-BL	1.7 (3)	1.1 (2.09)	0 (0)
Joint Pain-Baseline	1 (2.16)	1 (2)	0 (0)
Joint Pain-Post-BL	1.3 (2.14)	0.9 (1.06)	0 (0)
Muscle Aches-Baseline	0.5 (1.08)	0.5 (1)	0 (0)
Muscle Aches-Post-BL	1.2 (2.06)	0.8 (0.99)	0.3 (0.35)
Weakness of Body Parts-Baseline	0.6 (1.07)	1 (1.41)	0 (0)
Weakness of Body Parts-Post-BL	1.8 (2.3)	4 (2.74)	0 (0)
Burning Sensation in Hands or Feet-Baseline	0.8 (1.93)	2 (2.83)	0 (0)
Burning Sensation in Hands or Feet-Post-BL	2.3 (3.12)	2.6 (2.62)	0 (0)
Daytime Sleepiness-Baseline	0.5 (0.97)	0.8 (1.5)	0 (0)
Daytime Sleepiness-Post-BL	1.1 (1.52)	1.9 (1.91)	0 (0)
Dizziness/Lightheadedness-Baseline	0.2 (0.42)	0.5 (0.58)	0 (0)
Dizziness/Lightheadedness-Post-BL	0.4 (0.68)	0.8 (0.78)	0 (0)
Memory Loss-Baseline	0 (0)	0 (0)	0 (0)
Memory Loss-Post-BL	0.3 (0.87)	0 (0)	0 (0)
Numbness/Tingling-Baseline	0 (0)	0 (0)	0 (0)
Numbness/Tingling-Post-BL	0.7 (1.35)	0.2 (0.19)	0 (0)
Trouble Sleeping at Night-Baseline	1.3 (2.06)	1 (2)	3 (4.24)
Trouble Sleeping at Night-Post-BL	1.6 (1.81)	2.5 (2.28)	1 (1.41)
Trouble Thinking-Baseline	0 (0)	0 (0)	0 (0)
Trouble Thinking-Post-BL	0 (0.14)	0.1 (0.25)	0 (0)
Headache-Baseline	0.1 (0.32)	0.3 (0.5)	0 (0)
Headache-Post-BL	0.5 (0.6)	0.7 (0.55)	0 (0)
Pain-Baseline	0.8 (1.14)	1.3 (1.5)	0 (0)
Pain-Post-BL	2 (2.51)	2.6 (2.13)	0 (0)
Attend Paid Job-Baseline	1.1 (2.42)	2 (3.37)	0 (NA)
Attend Paid Job-Post-BL	3.8 (3.98)	3.7 (3.56)	0 (0)
Attend Social Activity-Baseline	0.6 (1.67)	1.3 (2.5)	0 (NA)
Attend Social Activity-Post-BL	1.8 (2.56)	3 (2.68)	0 (0)
Bathe or Dress-Baseline	0.2 (0.67)	0.5 (1)	0 (NA)
Bathe or Dress-Post-BL	1.3 (1.81)	1.4 (1.69)	0 (0)
Cook for Self-Baseline	0.8 (2.33)	1.8 (3.5)	0 (NA)
Cook for Self-Post-BL	1.6 (2.45)	2.6 (2.67)	0 (0)
Driving-Baseline	0.3 (1)	0.8 (1.5)	0 (NA)
Driving-Post-BL	1.2 (1.68)	2.2 (2.09)	0 (0)
Function Normally-Baseline	2.3 (3.2)	3.8 (4.35)	0 (NA)
Function Normally-Post-BL	2.9 (2.8)	3.8 (2.88)	0 (0)
Hard Work or Activity-Baseline	2.3 (2.87)	1.3 (1.15)	0 (NA)
Hard Work or Activity-Post-BL	3.9 (3.1)	5.3 (3.52)	0 (0)
Household Work-Baseline	1.6 (2.35)	2.3 (3.3)	0 (NA)
Household Work-Post-BL	2.8 (2.29)	4.2 (2.84)	0 (0)
Light Work or Activity-Baseline	0.6 (1.13)	0 (0)	0 (NA)
Light Work or Activity-Post-BL	2.6 (2.36)	3.4 (2.65)	0 (0)
Run-Baseline	2 (2.98)	0.7 (1.15)	0 (NA)
Run-Post-BL	3.8 (3.96)	5.9 (3.97)	0 (0)
Run Errands-Baseline	1.7 (3.32)	3.8 (4.35)	0 (NA)
Run Errands-Post-BL	2.5 (3)	4.6 (3.73)	0 (0)
Sit Up-Baseline	0.2 (0.67)	0.5 (1)	0 (NA)
Site Up-Post-BL	0 (0.14)	0.1 (0.25)	0 (0)
Stay Out of Bed-Baseline	0.2 (0.67)	0.5 (1)	0 (NA)
Stay Out of Bed-Post-BL	0.5 (1.11)	1.1 (1.66)	0 (0)
Walk-Baseline	0.8 (1.72)	0.5 (1)	0 (NA)
Walk-Post-BL	3.1 (3.19)	3.4 (2.26)	0 (0)
Crying/Feeling Like Crying-Baseline	0.1 (0.32)	0 (0)	0 (0)
Crying/Feeling Like Crying-Post-BL	0.2 (0.46)	0.2 (0.36)	0 (0)
Feeling Guilty-Baseline	0.1 (0.32)	0 (0)	0 (0)
Feeling Guilty-Post-BL	0.2 (0.72)	0 (0)	0 (0)
Feeling Helpless-Baseline	0 (0)	0 (0)	0 (0)
Feeling Helpless-Post-BL	0.4 (0.94)	0.8 (1.5)	0 (0)
Feeling Hopeless-Baseline	0 (0)	0 (0)	0 (0)
Feeling Hopeless-Post-BL	0.1 (0.43)	0.4 (0.75)	0 (0)
Feeling I Would Be Better Off Dead-Baseline	0 (0)	0 (0)	0 (0)
Feeling I Would Be Better Off Dead-Post-BL	0.2 (0.47)	0.2 (0.38)	0 (0)
Feeling Worthless-Baseline	0 (0)	0 (0)	0 (0)
Feeling Worthless-Post-BL	0.3 (0.69)	0.6 (1.13)	0 (0)
Lost Interest in People-Baseline	0.1 (0.32)	0 (0)	0 (0)
Lost Interest in People-Post-BL	0.4 (1.03)	0.6 (1.13)	0 (0)
Lost Interest in Pleasurable Activities-Baseline	0.1 (0.32)	0 (0)	0 (0)
Lost Interest in Pleasurable Activities-Post-BL	0.5 (1.3)	1.4 (2.14)	0 (0)
Nervous, Tense, Anxious-Baseline	1 (1.25)	0.8 (0.96)	1.5 (2.12)
Nervous, Tense, Anxious-Post-BL	0.6 (0.87)	0.9 (1.15)	0 (0)
Sad (Depressed)-Baseline	0 (0)	0 (0)	0 (0)
Sad (Depressed)-Post-BL	0.5 (0.95)	0.6 (1.25)	0 (0)
Worry-Baseline	1 (1.25)	0.8 (0.96)	1.5 (2.12)
Worry-Post-BL	0.6 (1.05)	0.8 (1.06)	0 (0)
Coughing-Baseline	1.6 (2.95)	2 (4)	3 (4.24)
Coughing-Post-BL	1 (2.29)	2.4 (3.79)	0 (0)
Shortness of Breath-Baseline	2.2 (2.86)	3.3 (3.59)	0 (NA)
Shortness of Breath-Post-BL	2.1 (2.7)	4 (3.47)	0 (0)
Wheezing-Baseline	1.2 (2.57)	2 (4)	0.5 (0.71)
Wheezing-Post-BL	1 (2.29)	2 (3.62)	0 (0)

5. Post-Hoc Outcome

Title	Median Progression Free Survival (PFS)
Description	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Progression is defined per RECIST criteria as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions. The median progression free survival is the parameter used to describe PFS.
Time Frame	PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever occurred first

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Screening Treatment Phase	Group A: Escalated Dose	Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.	Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
Measure Participants	12	4	2
Median (95% Confidence Interval) [Months]	11.37	5.77	NA

Adverse Events

Time Frame	Adverse events were collected when the patient began taking sorafenib until one month after the end of study treatment.
Adverse Event Reporting Description	Systematic assessment- subjects were assessed for adverse events every 4 weeks by either the research coordinator, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Screening Treatment Phase		Group A: Escalated Dose		Group B: Standard Dose
Arm/Group Description	After patients have signed informed consent and found to be eligible they will be started on standard dose sorafenib (800 mg/d) which constitutes the screening treatment phase. Patients who have been receiving treatment with commercial sorafenib outside of a clinical trial for < 2 weeks may also be able to participate in this trial provided all screening/baseline procedures are completed. During the screening treatment phase, commercial sorafenib will be prescribed. A patient will be eligible for randomization if (s)he successfully receives treatment with sorafenib for 4 weeks at 400 mg (po) bid (Study Weeks 1 through 4).		Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12. Sorafenib Escalated Dose : Patients randomized to Group A will receive sorafenib 600 mg bid for Weeks 5 through 8 (Dose Level 2). Patients who tolerate this dose through Week 8 will be further escalated to Dose Level 3 (800 mg po bid) for Weeks 9 through 12.		Eligible patients will be randomized 2:1 to either Group A (escalated dose regimen) or Group B (standard dose regimen). Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study. Sorafenib Standard Dose : Patients randomized to Group B will receive Dose Level 1 (sorafenib 400 mg po bid) until progression of disease, intolerable toxicity, patient refusal to continue with the study, or investigator decision to remove the patient from the study.
All Cause Mortality
	Screening Treatment Phase		Group A: Escalated Dose		Group B: Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Screening Treatment Phase		Group A: Escalated Dose		Group B: Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		1/4 (25%)		0/2 (0%)
Infections and infestations
Bronchitis	0/12 (0%)		1/4 (25%)		0/2 (0%)
Pneumonia	0/12 (0%)		1/4 (25%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/12 (0%)		1/4 (25%)		0/2 (0%)
Vascular disorders
Deep vein thrombosis	0/12 (0%)		1/4 (25%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Screening Treatment Phase		Group A: Escalated Dose		Group B: Standard Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		4/4 (100%)		2/2 (100%)
Eye disorders
Eye irritation	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)		1/4 (25%)		0/2 (0%)
Constipation	1/12 (8.3%)		1/4 (25%)		0/2 (0%)
Diarrhoea	2/12 (16.7%)		3/4 (75%)		2/2 (100%)
Dyspepsia	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Gastrooesophageal reflux disease	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Nausea	3/12 (25%)		1/4 (25%)		1/2 (50%)
Oral pain	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Vomiting	0/12 (0%)		0/4 (0%)		1/2 (50%)
General disorders
Asthenia	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Chills	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Face oedema	0/12 (0%)		1/4 (25%)		0/2 (0%)
Fatigue	3/12 (25%)		1/4 (25%)		1/2 (50%)
Influenza like illness	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Oedema	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Pyrexia	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Stomatitis	3/12 (25%)		0/4 (0%)		0/2 (0%)
Infections and infestations
Bronchitis	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Furuncle	0/12 (0%)		0/4 (0%)		1/2 (50%)
Investigations
Blood amylase increased	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Blood pressure increased	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Lipase increased	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Weight decreased	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Dehydration	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Hypophosphataemia	1/12 (8.3%)		1/4 (25%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)		0/4 (0%)		1/2 (50%)
Back pain	2/12 (16.7%)		0/4 (0%)		1/2 (50%)
Flank pain	0/12 (0%)		1/4 (25%)		0/2 (0%)
Myalgia	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Pain in extremity	1/12 (8.3%)		0/4 (0%)		1/2 (50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Nervous system disorders
Headache	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Psychiatric disorders
Insomnia	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Dysphonia	0/12 (0%)		1/4 (25%)		0/2 (0%)
Dyspnoea	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Nasal discomfort	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Oropharyngeal pain	2/12 (16.7%)		1/4 (25%)		0/2 (0%)
Productive cough	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Rhinorrhoea	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Acne	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Alopecia	1/12 (8.3%)		2/4 (50%)		1/2 (50%)
Dermatitis bullous	1/12 (8.3%)		0/4 (0%)		0/2 (0%)
Dry skin	3/12 (25%)		0/4 (0%)		1/2 (50%)
Erythema	2/12 (16.7%)		0/4 (0%)		1/2 (50%)
Nail disorder	0/12 (0%)		1/4 (25%)		1/2 (50%)
Palmar erythema	0/12 (0%)		1/4 (25%)		0/2 (0%)
Palmar-plantar erythrodysaesthesia syndrome	6/12 (50%)		2/4 (50%)		2/2 (100%)
Periorbital oedema	0/12 (0%)		1/4 (25%)		0/2 (0%)
Pruritus	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Rash	4/12 (33.3%)		0/4 (0%)		1/2 (50%)
Rash erythematous	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Rash generalised	2/12 (16.7%)		0/4 (0%)		0/2 (0%)
Vascular disorders
Hypertension	2/12 (16.7%)		0/4 (0%)		0/2 (0%)

Limitations/Caveats

The decision to close the study was made by the funder , Bayer HealthCare Pharmaceuticals, in collaboration with ACORN due to the low rate of accrual in light of study timelines and the lack of funds beyond the current level of support from Bayer.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Bayer with such presentation, abstract, or manuscript at least 30 days prior to its presentation or submission for the sole purpose of allowing Bayer to redact confidential information and protect any existing or future patients. The Principal Investigator shall acknowledge Bayer contributions where appropriate.